Why Stress Triggers Depression In Some People, Resilience In Others

Depending on your genetic makeup and a host of other variables, you’ll have a different reaction to stressful events from the people around you, and even your relatives. Some people naturally get energized by the challenge, even if it’s a frightening or intimidating one, and can’t wait to overcome it. Others feel dwarfed by the stress and just want to hide from it – this is called depression. Researchers and psychologists have long tried to tease apart why people have such different reactions to stress, and now a new study offers more clues about what's going on in the brain to explain this difference in people's responses.

There’s a group of neurons in the front of the brain – in the medial prefrontal cortex (mPFC) – that seems to be strongly linked to depression. Interestingly, this area of the brain is also known as the “me-center” of the brain – that is, cells in the area are active when you’re thinking about yourself, worrying about the future, worrying about your life, and day-dreaming. It’s part of the default mode network, which is just "on" when your mind isn't doing anything besides wandering about. It’s no surprise then that this area, the mPFC, is highly active in people who are depressed – since ruminating, worrying, and generally catastrophizing about one's life are central symptoms of depression.

(Photo credit: TheeErin)

But a team from Cold Spring Harbor wanted to see whether activity in the mPFC actually leads to depression or whether there’s some other mechanism at play. So they stressed out mice by shocking their paws at random intervals and not providing a way out. Psychology fans will recognize this as the “learned helplessness” model of depression: When the mice are later given a method of escape, some don’t even bother to take it – these are the “depressed” ones. Humans are very similar in that about 20% of people just shut down in response to repeated stress.

Says author Bo Li, “a subset of the mice, about 20%, will passively endure the shock. This helpless behavior is quite similar to what clinicians see in depressed individuals – an inability to take action to avoid or correct a difficult situation. Our work is focused on understanding why 20% of mice become depressed – just like why some people become depressed in response to stress while the majority of people do not."

It turned out, in the new study, that the subset of mice who exhibited the signs of depression had much greater activity in their mPFCs. Mice without depressive symptoms didn’t show this change in their brains.

This is interesting, but it still isn't proof that that the brain activity caused depression. To test this further, the team used a genetic method to tweak the genes of the mice to produce more activity in the mPFC. In other words, they were forcing that region of the brain to be active, and looking at how the mice behaved as a result.

"We artificially enhanced the activity of these neurons using a powerful method known as chemical genetics," says study author Bo Li. "The results were remarkable: once-strong and resilient mice became helpless, showing all of the classic signs of depression."

The researchers are excited by the findings, since they seem to confirm this biological basis for depression. They also say that methods like deep brain stimulation (DBS) are particularly promising since they target specific areas of the brain that are affected in depression. "We hope that our work will make DBS even more targeted and powerful," says Li, "and we are working to develop additional strategies based upon the activity of the mPFC to treat depression."

What else might work? “Classical antidepressants such as Prozac work to some extent,” says Li, “but the problem is that not all patients respond to it, and for those that are responsive, it takes a long time (~1 month) for Prozac to show the effects. It also has side effects.” And, he adds, some people never respond to antidepressants, which is why new, more effective methods are needed.

It’s certainly worth mentioning that there are simpler and less invasive ways to reduce activity in the mPFC. Mindfulness training and other forms of meditation have been shown to significantly reduce activity in the mPFC, as well as reduce the strength of the connection between the mPFC and areas of the brain that govern stress and anxiety. Some studies have even found that meditation is linked to structural changes in the areas related to "me-centered" worry thoughts. More and more studies are showing that meditation may be an effective method for treating depression, anxiety, PTSD, and other mental health issues.

The new study helps us understand more about what's going on in depression, but more will be needed before new treatments are developed. In the meantime, do what we know to be effective: Exercise, meditation, talk therapy, and medication if necessary. The science will catch up -- but it may take a while. So do what works now.